The goals of this project are to acquire a deeper understanding of how the allsoteric enzyme aspartate transcarbamoylase can control the rate of a metabolic pathway. Aspartate transcarbamoylase catalyzes the first reaction in the pyrimidine biosyntheses pathway, the reaction of carbamoyl phosphate and aspartate to form N-carbamoyl-L-aspartate and inorganic phosphate. Even the extensive X-ray structures of aspartate transcarbamoylase provides only a static picture of this most complex enzyme. Our laboratory has been involved in the study of mutant versions of aspartate transcarbamoylase containing single amino acid substitutions by biochemical and structural means. Time on the Y-MP C90 at PSC is being requested in order to carry out the refinement of the X-ray crystallographic data on 4-5 mutant versions of the enzyme. The project involves using the program XPLOR to refine the X-ray crystallography data on two mutant versions of the enzyme for which data is already available, and at least three others for which data will be collected. Local computer facilities are not capable of carrying out these calculations in reasonable times. Correlations will then be made between the functional changes induced by the amino acid substitution and the three-dimensional structure of the mutant enzymes. This work will not only be important for the understanding of this particular system, but more importantly for formulating general concepts about enzyme catalysis, and the mechanisms of homotropic and heterotropic cooperativity.